Protocol for the Examination of Specimens From Patients With Tumors of the Brain/Spinal Cord

Protocol for the Examination of Specimens From Patients With Tumors of the Brain/Spinal Cord Protocol applies to all primary neoplasms of the brain/ spinal cord/peripheral nerve and pituitary. Metastatic tumors are not included. No AJCC/UICC TNM Staging System Protocol web posting date: November 2011 Procedures Biopsy/Resection Authors Joseph E. Parisi, MD Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Dylan V. Miller, MD Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Philip J. Boyer, MD, PhD Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado Daniel J. Brat, MD, PhD Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia Elizabeth J. Cochran, MD Department of Pathology and Neurologic Science, Rush University Medical Center, Chicago, Illinois Mark L. Cohen, MD Department of Pathology, Case Western Reserve University, Cleveland, Ohio Bette K. DeMasters, MD Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado David Dolinak, MD Travis County Medical Examiner Office, Austin, Texas Rodney D. McComb, MD Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska Roger E. McLendon, MD Department of Pathology, Duke University Medical Center, Durham, North Carolina Suzanne Z. Powell, MD Department of Pathology, The Methodist Hospital, Houston, Texas Richard A. Prayson, MD Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio Harry V. Vinters, MD Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California Anthony T. Yachnis, MD Department of Pathology, Shands Hospital at University of Florida, Gainsville, Florida For the Members of the Cancer Committee, College of American Pathologists Previous contributors: Gary S. Pearl, MD, PhD; Saeid Movahedi-Lankarani, MD; Nancy C. Karpinski, MD; Kyung-Whan Min, MD; Steven C. Bauserman, MD; Lawrence A. Hansen, MD; Charles Kerber, MD

2011 College of American Pathologists (CAP). All rights reserved. The College does not permit reproduction of any substantial portion of these protocols without its written authorization. The College hereby authorizes use of these protocols by physicians and other health care providers in reporting on surgical specimens, in teaching, and in carrying out medical research for nonprofit purposes. This authorization does not extend to reproduction or other use of any substantial portion of these protocols for commercial purposes without the written consent of the College. The CAP also authorizes physicians and other health care practitioners to make modified versions of the Protocols solely for their individual use in reporting on surgical specimens for individual patients, teaching, and carrying out medical research for non-profit purposes. The CAP further authorizes the following uses by physicians and other health care practitioners, in reporting on surgical specimens for individual patients, in teaching, and in carrying out medical research for non-profit purposes: (1) Dictation from the original or modified protocols for the purposes of creating a text-based patient record on paper, or in a word processing document; (2) Copying from the original or modified protocols into a text-based patient record on paper, or in a word processing document; (3) The use of a computerized system for items (1) and (2), provided that the Protocol data is stored intact as a single text-based document, and is not stored as multiple discrete data fields. Other than uses (1), (2), and (3) above, the CAP does not authorize any use of the Protocols in electronic medical records systems, pathology informatics systems, cancer registry computer systems, computerized databases, mappings between coding works, or any computerized system without a written license from CAP. Applications for such a license should be addressed to the SNOMED Terminology Solutions division of the CAP. Any public dissemination of the original or modified Protocols is prohibited without a written license from the CAP. The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations of surgical specimens. The College regards the reporting elements in the Surgical Pathology Cancer Case Summary portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the required data elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document. The inclusion of a product name or service in a CAP publication should not be construed as an endorsement of such product or service, nor is failure to include the name of a product of service to be construed as disapproval. 2

CAP Brain/Spinal Cord Protocol Revision History Version Code The definition of the version code can be found at www.cap.org/cancerprotocols. Version: Summary of Changes The following changes have been made since the June 2008 release. Biopsy/Resection Tumor Site Cranial or peripheral nerve was changed to Peripheral nerve. Histologic Type and Tumors of Cranial and Paraspinal Nerves Malignant perineurioma (WHO grade III) was added. Mesenchymal (Nonmeningothelial) Tumors Osteoma and Malignant hemangiopericytoma were added. Tumors of the Sellar Region Craniopharyngioma (WHO grade I) was added. Important Note This protocol should be applied to all primary neoplasms of the brain/spinal cord/peripheral nerve and pituitary, and it should be applied at initial biopsy/resection. Metastatic tumors are not included. There is no American Joint Committee on Cancer / International Union Against Cancer TNM classification system for primary nervous system neoplasms. The World Health Organization (WHO) grading system is recommended. 3

CAP Approved Surgical Pathology Cancer Case Summary Protocol web posting date: November 2011 BRAIN/SPINAL CORD: Biopsy/Resection Select a single response unless otherwise indicated. + History of Previous Tumor/Familial Syndrome (Note A) + None known + Known (specify, if known: ) + Not specified Specimen Type/Procedure (Note B) Open biopsy Resection Stereotactic biopsy Other (specify): Not specified Specimen Handling (select all that apply) (Note C) Squash/smear/touch preparation Frozen section Tissue for electron microscopy Frozen tissue Unfrozen for routine permanent paraffin sections Other (specify): Not specified + Specimen Size (Note D) + Greatest dimension: cm + Additional dimensions: x cm (for fragmented tissue, an aggregate size may be given) + Cannot be determined (see Comment) Laterality Right Left Bilateral Not specified Not applicable + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 4

CAP Approved Tumor Site (select all that apply) (Note E) Skull + Specify further (eg, frontal, parietal, temporal, occipital), if known: Dura + Specify further (eg, cerebral [convexity/lobe, falx, tentorium, sphenoid wing, skull base, other], spinal or other), if known: Leptomeninges + Specify further (eg, cerebral [convexity/lobe], spinal, or other), if known: Brain/cerebrum + Specify lobe(s) (eg, frontal, temporal, parietal, occipital), if known: Brain, other: Basal ganglia Thalamus Hypothalamus Pineal Cerebellum Cerebellopontine angle Suprasellar Sella Other (specify, if known: ) Cranial nerve + Specify I-II, if known: Ventricle + Specify lateral, third, fourth, cerebral aqueduct, if known: Brainstem + Specify midbrain, pons, or medulla, if known: Spine (vertebral column) + Specify bony level (eg, C5, T2, L3), if known: Spinal Cord + Specify bony level (eg, C5, T2, L3), if known: + Specify spinal location (eg, extradural, intradural-extramedullary, intramedullary, conus medullaris, filum terminale), if known: Spinal nerve root(s) + Specify bony level (eg, C5, T2, L3), if known: + Specify location (eg, intradural, foramen), if known: Peripheral nerve + Specify site, if known: Ganglion + Specify site, if known: Other (specify): Not specified Histologic Type and (applicable World Health Organization [WHO] classification and grade) (select all that apply) (Note F, Note G) Astrocytic Tumors Pilocytic astrocytoma (WHO grade I) Pilomyxoid astrocytoma (WHO grade II) Subependymal giant cell astrocytoma (WHO grade I) Pleomorphic xanthoastrocytoma (WHO grade II) Pleomorphic xanthoastrocytoma with anaplastic features (WHO grade not assigned) + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 5

CAP Approved Diffuse astrocytoma (WHO grade II) Fibrillary astrocytoma (WHO grade II) Protoplasmic astrocytoma (WHO grade II) Gemistocytic astrocytoma (WHO grade II) Anaplastic astrocytoma (WHO grade III) Glioblastoma (WHO grade IV) Giant cell glioblastoma (WHO grade IV) Gliosarcoma (WHO grade IV) Gliomatosis cerebri (usually WHO grade III; diagnosis requires clinical-pathological correlation) Astrocytoma, not otherwise characterized (WHO grades I-IV) Oligodendroglial Tumors Oligodendroglioma (WHO grade II) Anaplastic oligodendroglioma (WHO grade III) Oligoastrocytic Tumors (mixed glioma) Oligoastrocytoma (WHO grade II) Anaplastic oligoastrocytoma (WHO grade III) Ependymal Tumors Subependymoma (WHO grade I) Myxopapillary ependymoma (WHO grade I) Ependymoma (WHO grade II) Cellular ependymoma (WHO grade II) Papillary ependymoma (WHO grade II) Clear cell ependymoma (WHO grade II) Tanycytic ependymoma (WHO grade II) Anaplastic ependymoma (WHO grade III) Choroid Plexus Tumors Choroid plexus papilloma (WHO grade I) Atypical choroid plexus papilloma (WHO grade II) Choroid plexus carcinoma (WHO grade III) Other Neuroepithelial Tumors Astroblastoma (WHO grade not assigned) Chordoid glioma of the third ventricle (WHO grade II) Angiocentric glioma (WHO grade I) Neuronal and Mixed Neuronal-Glial Tumors Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos) (WHO grade I) Desmoplastic infantile astrocytoma/ganglioglioma (WHO grade I) Dysembryoplastic neuroepithelial tumor (WHO grade I) Gangliocytoma (WHO grade I) Ganglioglioma (WHO grade I) Anaplastic ganglioglioma (WHO grade III) Central neurocytoma (WHO grade II) Extraventricular neurocytoma (WHO grade II) Cerebellar liponeurocytoma (WHO grade II) Papillary glioneuronal tumor (PGNT) (WHO grade I) Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) (WHO grade I) Paraganglioma of the spinal cord (WHO grade I) + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 6

CAP Approved Tumors of the Pineal Region Pineal parenchymal tumors Pineocytoma (WHO grade I) Pineal parenchymal tumor of intermediate differentiation (WHO II-III) Pineoblastoma (WHO grade IV) Papillary tumor of the pineal region (WHO grade II-III) Embryonal Tumors Medulloblastoma, not otherwise characterized (WHO grade IV) Desmoplastic/nodular medulloblastoma (WHO grade IV) Medulloblastoma with extensive nodularity (WHO grade IV) Anaplastic medulloblastoma (WHO grade IV) Large cell medulloblastoma (WHO grade IV) Central nervous system (CNS) primitive neuroectodermal tumor (PNET) (WHO grade IV) Medulloepithelioma (WHO grade IV) Neuroblastoma (WHO grade IV) Ganglioneuroblastoma (WHO grade IV) Ependymoblastoma (WHO grade IV) Atypical teratoid/rhabdoid tumor (WHO grade IV) Tumors of Cranial and Paraspinal Nerves Schwannoma (WHO grade I) Cellular (WHO grade I) Plexiform (WHO grade I) Melanotic (WHO grade I) Neurofibroma (WHO grade I) Plexiform (WHO grade I) Perineurioma (WHO grade I) Intraneural perineurioma (WHO grade I) Soft tissue perineurioma (WHO grade I) Malignant perineurioma (WHO grade III) Ganglioneuroma (WHO grade I) Malignant peripheral nerve sheath tumor (MPNST) (WHO grade II-IV) (Note H, Note I) Epithelioid (WHO grade II-IV) MPNST with divergent mesenchymal and/or epithelial differentiation (WHO grade II-IV) Tumors of the Meninges/Meningothelial Cells Meningioma (WHO grade I) Meningothelial (WHO grade I) Fibrous (fibroblastic) (WHO grade I) Transitional (mixed) (WHO grade I) Psammomatous (WHO grade I) Angiomatous (WHO grade I) Microcystic (WHO grade I) Secretory (WHO grade I) Lymphoplasmacyte-rich (lymphoplasmacytic) (WHO grade I) Metaplastic (WHO grade I) Atypical meningioma (WHO grade II) Clear cell meningioma (WHO grade II) Chordoid meningioma (WHO grade II) Anaplastic meningioma (WHO grade III) + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 7

CAP Approved Papillary meningioma (WHO grade III) Rhabdoid meningioma (WHO grade III) Other (specify): Mesenchymal (Nonmeningothelial) Tumors (Note I) Lipoma Angiolipoma Hibernoma Liposarcoma (intracranial) Solitary fibrous tumor Fibrosarcoma Malignant fibrous histiocytoma Leiomyoma Leiomyosarcoma Rhabdomyoma Rhabdomyosarcoma Chondroma Chondrosarcoma Osteoma Osteosarcoma Osteochondroma Hemangioma Epithelioid hemangioendothelioma Hemangiopericytoma Malignant hemangiopericytoma Angiosarcoma Kaposi sarcoma Chordoma Mesenchymal, nonmeningothelial tumor, other (specify type, if possible): Sarcoma, primary CNS (specify type, if possible): Primary Melanotic Tumors Diffuse melanocytosis Melanocytoma Malignant melanoma Meningeal melanomatosis Tumors of Uncertain Histogenesis Hemangioblastoma (WHO grade I) Lymphoma and Hematopoietic Tumors Malignant lymphoma (specify type, if possible): Plasmacytoma Granulocytic sarcoma Hematopoietic neoplasm, other (specify type, if possible): + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 8

CAP Approved Germ Cell Tumors Germinoma Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratoma, mature Teratoma, immature Teratoma with malignant transformation Malignant mixed germ cell tumor (specify components, eg, germinoma, embryonal, yolk sac, choriocarcinoma, teratoma): Tumors of the Sellar Region Craniopharyngioma (WHO grade I) Craniopharyngioma, adamantinomatous (WHO grade I) Craniopharyngioma, papillary (WHO grade I) Granular cell tumor (WHO grade I) Pituicytoma (WHO grade I) Spindle cell oncocytoma (WHO grade I) Pituitary adenoma (specify nonfunctional or hormone expression, if known): Pituitary carcinoma Pituitary hyperplasia Other (specify): Other/Nonclassifiable Other(s) (specify): Malignant neoplasm, type cannot be determined Histologic (WHO histologic grade) (Note G) Not applicable Cannot be determined WHO grade I WHO grade II WHO grade III WHO grade IV WHO grade not assigned Other (specify): Margins (for resections of malignant peripheral nerve sheath tumors only) (Note H) Cannot be assessed Margins not involved by tumor Margins involved by tumor + Specify, if possible: + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 9

CAP Approved + Ancillary Studies (select all that apply) + None performed + Immunohistochemistry (specify): + Electron microscopy + Molecular genetic studies (specify): (Note J) + 1p deletion identified + 1p deletion not identified + 19q deletion identified + 19q deletion not identified + Other (specify): + Other (specify): + Additional Pathologic Findings + Specify: + Comment(s): + Data elements preceded by this symbol are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. 10

Background Documentation Explanatory Notes A. Relevant History Patient Age Patient age may be critically important for predicting tumor behavior. For example, patient age is predictive of survival in many malignant CNS neoplasms. For diffusely infiltrating astrocytomas, age and histologic grade are the two strongest predictors of patient outcome, with patient age greater than 50 years and high-grade histologic features serving as negative indicators. 1-4 Duration of Symptoms A long clinical history of CNS symptoms or seizures prior to the diagnosis of a CNS tumor is suggestive of origin from a slowly growing neoplasm. Alternatively, a sudden onset of clinical symptoms or a rapidly progressive neurological deficit may be indicative of a high-grade tumor, hemorrhage, infarct, active demyelinating disease, or edema associated with some other benign or low-grade lesion. Previous Diagnoses or CNS Biopsies Knowledge of the presence or absence of previous intracranial or extracranial disease (eg, immunosuppression, previous CNS or other primary neoplasm) is essential for specimen interpretation. If a previous tumor is included in the differential diagnosis, it is useful to have microscopic slides of the lesion available for review and comparison. Preoperative Treatment Knowledge of preoperative treatment, including radiation therapy, corticosteroid therapy, chemotherapy, and other therapy, is helpful for specimen interpretation. In particular, prior radiation therapy or radiosurgery may alter the interpretation of specimens in which there are increased cellular atypia, decreased proliferative activity, or large areas of radiation-induced change (eg, coagulative [nonpalisading] necrosis, vascular hyalinization, and gliosis). Family History of Cancer or Primary CNS Tumors Several genetic conditions/syndromes are associated with an increased predisposition to the development of certain brain neoplasms (eg, neurofibromatosis types 1 and 2, Turcot/Lynch, tuberous sclerosis, von Hippel-Lindau, Cowden, Li-Fraumeni, and Gorlin syndromes). Relevant Radiographic Imaging Features Knowledge of neuroimaging features is extremely helpful in specimen interpretation. A differential diagnosis may be generated based on patient age, tumor location, and neuroimaging features. Neuroimaging also can be helpful in providing correlation with or highlighting discrepancy with pathologic diagnosis (eg, contrast enhancement with hypocellularity). A close collaboration with the neuroradiologist and neurosurgeon is essential. B. Specimen Type/Procedure It is useful to know if the specimen was procured by open craniotomy or stereotactic biopsy. Since tumors may be heterogeneous, adequate sampling is an issue. The reliability of the prognostic information derived from such specimens may vary depending on how the specimen was obtained. C. Specimen Handling, Triage, and Special Procedures It may be necessary to divide biopsy/resection tissue into portions for the following procedures: Squash/smear/touch preparations Frozen sections Unfrozen routine permanent paraffin sections (essential to avoid artifacts) Electron microscopy (retain a small portion in glutaraldehyde, or "embed and hold" for electron microscopy, if necessary) 11

Background Documentation Frozen tissue, for possible molecular diagnostic studies (freeze fresh tissue as soon as possible and store) Other (microbiology, flow cytometry, cytogenetics, molecular diagnostics) Since cellular details are very important in interpreting CNS neoplasms, previously frozen tissue with its inherent artifacts is suboptimal, especially for subclassifying and grading gliomas. Recommendations for optimally freezing and cutting frozen sections from tissue from the brain and spinal cord have been published. 5 It is imperative to retain tissue that has not been previously frozen for permanent sections. Avoid using sponges in cassettes because they produce angular defects that resemble vascular/luminal spaces in the final sections. Wrapping small biopsies in lens paper, or placement into agar or into tissue sacs prior to submitting in cassettes, is recommended. If biopsy frozen and permanent sections are nondiagnostic, tissue that was retained in glutaraldehyde may be submitted for additional paraffin sections. If touch preparations are used, the presence of cells with delicate processes on smear/ squash preparations is suggestive of a primary CNS neoplasm. The formation of processes and cytoplasmic fibrillarity may be seen in reactive astrocytosis. The identification of macrophages is important since a macrophage-rich lesion is more likely a subacute infarct or demyelination, rather than a neoplasm. If an infectious etiology is suspected, the neurosurgeon should be alerted to submit a fresh sample to microbiology to be processed for bacterial, fungal, and/or viral cultures. If a lymphoproliferative disorder is suspected and sufficient tissue is available, a portion of fresh tissue should be set aside for appropriate workup. D. Specimen Size For most CNS tumors, specimen size is of limited significance, with optimal preservation and processing of greater importance. In heterogeneous lesions, issues of tissue sampling may become important. E. Primary Tumor Location and Size Since the anatomic site of a neoplasm may correlate with tumor type and prognosis, it should be recorded, if known. F. Histologic Type Classification of tumors should be made according to the WHO classification of tumors of the nervous system 6,7 whenever possible. G. Histologic The WHO grading 6,7 of some of the more common CNS tumors is shown in Table 1. There is no formal TNM-based classification and staging system for CNS tumors. 12

Background Documentation Table 1. WHO Grading System for some of the More Common Tumors of the CNS Tumor Group Tumor Type Astrocytic tumors Diffuse astrocytoma Anaplastic astrocytoma Glioblastoma Pilocytic astrocytoma Pilomyxoid astrocytoma Subependymal giant cell astrocytoma Pleomorphic xanthoastrocytoma Oligodendrogliomas Oligodendroglioma Anaplastic oligodendroglioma Oligoastrocytomas Oligoastrocytoma Anaplastic oligoastrocytoma Ependymal tumors Ependymoma Anaplastic ependymoma Subependymoma Myxopapillary ependymoma Choroid plexus tumors Choroid plexus papilloma Atypical choroid plexus papilloma Choroid plexus carcinoma Other neuroepithelial tumors Angiocentric glioma Chordoid glioma of the third ventricle Neuronal-glial tumors Gangliocytoma Desmoplastic infantile ganglioglioma/ astrocytoma (DIG) Dysembryoplastic neuroepithelial tumor (DNET) Ganglioglioma Anaplastic ganglioglioma Central neurocytoma Extraventricular neurocytoma Cerebellar liponeurocytoma Papillary glioneuronal tumor (PGNT) Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) Paraganglioma of the spinal cord I II III IV 13

Background Documentation Tumor Group Tumor Type Pineal parenchymal tumors Pineocytoma Pineal parenchymal tumor of intermediate differentiation Pineoblastoma Papillary tumor of the pineal region I II Embryonal tumors Medulloblastoma Cranial and peripheral nerve tumors CNS primitive neuroectodermal tumor Medulloepithelioma Neuroblastoma Ganglioneuroblastoma Ependymoblastoma Atypical teratoid/rhabdoid tumor Schwannoma Neurofibroma Perineurioma Malignant peripheral nerve sheath tumors (MPNST) Meningeal tumors Meningioma Atypical meningioma Clear cell meningioma Chordoid meningioma Anaplastic meningioma Papillary meningioma Rhabdoid meningioma III IV Mesenchymal tumors 8,9 (Named as soft tissue counterpart) Tumors of uncertain histogenesis Hemangiopericytoma Hemangioblastoma After patient age, tumor histology and grade have been shown to be the strongest predictors of clinical course in selected CNS astrocytomas. Several grading systems for diffusely infiltrating astrocytomas are based on their ability to define distinct groups with significantly different survivals. The WHO uses a 3- tiered grading system (modified St. Anne-Mayo) for diffuse astrocytomas 6,7 (Table 2). 14

Background Documentation Table 2. WHO Grading System for Diffuse Infiltrating Astrocytomas WHO WHO Designation Histologic Criteria II Diffuse astrocytoma 1 criterion: usually nuclear atypia III Anaplastic astrocytoma 2 criteria: usually nuclear atypia and mitoses IV Glioblastoma 3 criteria: usually nuclear atypia, mitoses, and endothelial proliferation and/or necrosis H. Margins With the exception of malignant peripheral nerve sheath tumors, resection margins provide no prognostic information and generally are not required for most CNS neoplasms. I. Mesenchymal Tumors Mesenchymal tumors vary widely in grade, from benign tumors (WHO grade I) to highly malignant sarcomas (WHO grade III to IV). The classification and grading of these lesions is performed as for the corresponding tumor of soft tissue and bone, as detailed in the WHO monograph, Tumours of Soft Tissue and Bone, 8 and the College of American Pathologists bone and soft tissue cancer protocol. 9 J. Molecular Genetic Studies Recent studies have shown that combined 1p and 19q deletions in oligodendrogliomas are associated with enhanced chemoresponsiveness and improved survival. 10-12 In addition, several other rapidly emerging molecular markers are providing useful diagnostic and prognostic information. For example, EGFR amplification may be useful in distinguishing high-grade astrocytoma from anaplastic oligodendroglioma; n-myc amplification has prognostic significance in medulloblastomas; and INI1 studies are useful in the diagnosis of atypical teratoid/rhabdoid tumor. References 1. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4 th ed. New York: Churchill Livingstone; 2002. 2. Ironside JW, Moss TH, Louis DN, et al. Diagnostic Pathology of Nervous System Tumours. New York: Churchill Livingstone; 2002. 3. McLendon RE, Rosenblum MK, Bigner DD, eds. Russell and Rubinstein's Pathology of Tumors of the Nervous System. 7 th ed. New York: Hodder Arnold; 2006. 4. Burger PC, Scheithauer BW. Atlas of Tumor Pathology, Third Series. Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology; 2003. 5. Burger PC, Nelson JS. Stereotactic brain biopsies: specimen preparation and evaluation. Arch Pathol Lab Med. 1997;121:477-480. 6. Klieheus P, Cavenee WK, eds. Pathology and Genetics of Tumors of the Nervous System. Lyon, France: IARC Press; 2007. World Health Organization Classification of Tumors. 7. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. WHO Classification of Tumours of the Central Nervous System. Lyon, France: IARC Press; 2007. 8. Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics. Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002: 12-18. 9. Rubin BP, Fletcher CD, Inwards C, et al. College of American Pathologists. Protocol for the examination of specimens from patients with soft tissue tumors of intermediate malignant potential, malignant soft tissue tumors, and benign/locally aggressive and malignant bone tumors. Arch Pathol Lab Med. 2006;130:1616-1629. 15

Background Documentation 10. Cairncross JG, Ueki K, Zlatescu C, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst. 1998;90:1473-1479. 11. Smith JS, Perry A, Borell TJ, et al. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol. 2000;18:636-645. 12. Jenkins RB, Blair H, Ballman KV, et al. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res. 2006;66:9852-9861. 16